Cardiac disease includes a host of diseases and disorders of the heart, including congenital heart disease, aortic aneurysms, aortic dissections, arrhythmia, cardiomyopathy, and congestive heart failure. Congestive heart failure, in particular, occurs when the heart is unable to maintain an adequate circulation of blood in the tissues of the body or to pump out the venous blood returned to it. This weakening of the heart prevents it from circulating a sufficient quantity of oxygen to the body's tissues. Cardiac diseases that involve contractility, e.g., congestive heart failure, depend on the regulation of the contraction/relaxation cycle of muscle cells in the heart.
ATPase, Ca++ transporting, cardiac muscle, slow twitch 2 (ATP2A2) encodes a sacroplasmic reticulum Ca++-ATPase (SERCA), which is an intracellular pump located in the sarcoplasmic or endoplasmic reticula of muscle cells. ATP2A2 maintains a low cytoplasmic concentration of Ca2+ ions through hydrolysis of ATP coupled with the translocation of calcium from the cytosol into the sarcoplasmic reticulum lumen. This transport of calcium is important for regulating the contraction/relaxation cycle of muscle cells. Mice harboring mutant forms of ATP2A2 display several cardiac issues due to decreased ATP2A2 activity. Specifically, defects occur in heart rate, cardiac stroke volume, cardiac output, cardiac hypertrophy, and congestive heart failure.